This chapter discusses potential mechanisms linking obesity to gestational diabetes mellitus (GDM) and pre-eclampsia (PE). The molecular mechanisms leading to excess hepatic fat accumulation remain elusive. In pregnancy, maternal fat metabolism is of increasing importance as gestation advances in order to spare carbohydrate for the fetus. There is a well-described association between PE and subsequent cardiovascular disease (CVD) risk, especially for those women with a history of early severe PE. Substantial weight loss via bariatric surgery can considerably lessen the risk of PE as demonstrated in a recent retrospective analysis in which risk for PE or eclampsia was 80% lower in the same women after surgery. Lifestyle interventions in obese pregnant women may also prove effective. Successful placentation is essential for healthy pregnancy outcome, and in PE partial failure of trophoblast invasion is likely to play a major role in the disease process.